Decreased intraindividual HLA class I expression is due to reduced transcription in advanced melanoma and does not correlate with HLA-G expression.
Decreased intraindividual HLA class I expression is due to reduced transcription in advanced melanoma and does not correlate with HLA-G expression.
复制标题
个体内 HLA I 类表达减少是由于晚期黑色素瘤中转录减少所致，与 HLA-G 表达无关。
DOI：
--
复制
发表时间：
2001
影响因子：
6.5
通讯作者：
R. Dummer
中科院分区：
文献类型：
--
作者：
J. Willers;M. Urosevic;E. Laine;R. Geertsen;T. Kündig;G. Burg;R. Dummer
与HLA I类分子结合的内源性合成肽的呈递允许CD 8（+）淋巴细胞的活化。肿瘤细胞通常不能呈递抗原肽，导致转移细胞的免疫逃逸。本研究的目的是阐明可能的分子机制，导致黑色素瘤抗原呈递减少。黑色素瘤细胞短期培养物的基因型和表型HLA分型的序列特异性引物聚合酶链反应和补体介导的微量淋巴细胞毒性试验，分别。进行HLA-A2和HLA-A3同种特异性的流式细胞术分析以确认分型结果。采用实时荧光定量逆转录聚合酶链反应（LightCycler）检测HLA-A、HLA-B和非经典HLA-G基因的转录水平。我们发现在所有检测的转移瘤中，18%（HLA-A）和53%（HLA-B）的HLA蛋白丢失或下调。然而，基因组分析显示，存在相应的HLA I类基因的7例中有6例。在基因转录水平上，我们观察到HLA-A、HLA-B和HLA-G mRNA表达的差异调节。经典型和非经典型HLA基因转录水平之间无相关性，但经典型HLA基因转录水平与蛋白表达水平相对应。此外，在三个个体的疾病进展期间，在黑素瘤转移中观察到HLA I类基因转录的总体减少量。我们假设，有一个转录调节HLA I类基因的表达在黑色素瘤细胞。这些数据表明，旨在激活特异性细胞毒性T淋巴细胞的治疗方法在早期疾病中最成功。
The presentation of endogenously synthesized peptides in association with HLA class I molecules allows the activation of CD8(+) lymphocytes. Tumor cells often fail to present antigenic peptides resulting in the immune escape of metastasizing cells. The aim of this study was to elucidate possible molecular mechanisms leading to reduced antigen presentation in melanoma. Melanoma cell short-time cultures were genotypically and phenotypically HLA-typed by sequence-specific primer polymerase chain reaction and complement-mediated microlymphocytotoxicity assays, respectively. Flow cytometric analysis of HLA-A2 and HLA-A3 allospecificities were performed to confirm typing results. Transcriptional levels of classical HLA-A, HLA-B genes and nonclassical HLA-G genes were detected using quantitative real-time reverse transcriptase polymerase chain reaction (LightCycler). We found loss or downregulation of HLA proteins in 18% (for HLA-A) and 53% (for HLA-B) of all tested metastases. Genomic analysis, however, revealed the presence of the corresponding HLA class I gene in six out of seven cases. On the level of gene transcription we observed a differential regulation of HLA-A, HLA-B, and HLA-G mRNA expression. There was no correlation between classical and nonclassical HLA gene transcription, but the transcriptional levels of classical HLA corresponded to the protein expression levels. Furthermore, an overall reduced amount of HLA class I gene transcription was observed in melanoma metastases during disease progression in three individuals. We postulate that there is a transcriptional regulation of HLA class I gene expression in melanoma cells. These data suggest that treatment approaches aimed at activating specific cytotoxic T lymphocytes are most successful in early disease.
登录
查看更多内容
影响因子：
15.9
作者：
DURSO, CM;WANG, ZG;FERRONE, S
通讯作者：
FERRONE, S
影响因子：
11.2
作者：
T. Kageshita;Zhigang Wang;L. Calorini;A. Yoshii;T. Kimura;T. Ono;S. Gattoni‐Celli;S. Ferrone
通讯作者：
T. Kageshita;Zhigang Wang;L. Calorini;A. Yoshii;T. Kimura;T. Ono;S. Gattoni‐Celli;S. Ferrone
黑色素瘤细胞 SK-MEL-29.1.22 和 SK-MEL-29.1.29 造成的 HLA-A2 抗原丢失的分子分析。
DOI：
--
发表时间：
1998
期刊：
Cancer research.
影响因子：
--
作者：
Wang,Z;Seliger,B;Mike,N;Momburg,F;Knuth,A;Ferrone,S
通讯作者：
Ferrone,S
黑色素瘤患者局部转移灶中 HLA 抗原的水平和疾病的临床病程。
影响因子：
11.2
作者：
vanDuinen,SG;Ruiter,DJ;Broecker,EB;vanderVelde,EA;Sorg,C;Welvaart,K;Ferrone,S
通讯作者：
Ferrone,S